Fitness inference from short-read data: within-host evolution of a reassortant H5N1 influenza virus

Illingworth, C. J.R. (2015) Fitness inference from short-read data: within-host evolution of a reassortant H5N1 influenza virus. Molecular Biology and Evolution, 32(11), pp. 3012-3026. (doi: 10.1093/molbev/msv171) (PMID:26243288) (PMCID:PMC4651230)

Abstract

We present a method to infer the role of selection acting during the within-host evolution of the influenza virus from short-read genome sequence data. Linkage disequilibrium between loci is accounted for by treating short-read sequences as noisy multilocus emissions from an underlying model of haplotype evolution. A hierarchical model-selection procedure is used to infer the underlying fitness landscape of the virus insofar as that landscape is explored by the viral population. In a first application of our method, we analyze data from an evolutionary experiment describing the growth of a reassortant H5N1 virus in ferrets. Across two sets of replica experiments we infer multiple alleles to be under selection, including variants associated with receptor binding specificity, glycosylation, and with the increased transmissibility of the virus. We identify epistasis as an important component of the within-host fitness landscape, and show that adaptation can proceed through multiple genetic pathways.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Illingworth, Dr Chris
• Authors: Illingworth, C. J.R.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity; College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Virus Research
• Journal Name: Molecular Biology and Evolution
• Publisher: Oxford University Press
• ISSN: 0737-4038
• ISSN (Online): 1537-1719
• Published Online: 04 August 2015
• Copyright Holders: Copyright © 2015 The Authors
• First Published: First published in Molecular Biology and Evolution 32(11): 3012-3026
• Publisher Policy: Reproduced under a Creative Commons License